The compound 2(R)-2-methyl-3-dimethylaminopropiophenone (d-DAMP) is useful as an intermediate in the stereospecific synthesis of .alpha.-d-4-dimethylamino -1,2-diphenyl-3-methyl-2-butanol (d-oxyphene) which, in turn, is an intermediate in the synthesis of d-propoxyphene, the propionyl ester of d-oxyphene.
Previously, intermediate d-oxyphene has been produced by resolving d-DAMP through crystallization of stereospecific tartate salts and then by reacting the d-DAMP with benzylmagnesium chloride. Pohland, et al., J. Org. Chem., Vol. 28, p 2483 (1963). Alternatively, intermediate d-oxyphene has been produced using a tetrasubstituted epoxy alcohol intermediate. Erickson, T., "Asymetric Synthesis of Darvon Alcohol," J. Org. Chem., Vol. 51, p. 934-935 (1986). These procedures, by which intermediate d-oxyphene has previously been synthesized, are lengthy, inefficient and expensive ways to produce the end product d-propoxyphene.
The end product d-propoxyphene is recognized and accepted as possessing effective analgesic qualities in humans, whereas, 1-propoxyphene does not possess these same qualities. Pohland, A., and Sullivan, H.R, "Preparation of .alpha.-d- and .alpha.-1-4-Dimethylamino-1,2-diphenyl-3-methyl-2-propionyloxy butane," J. Am. Chem. Soc., Vol. 77, p 3400 (1955).
When producing a stereospecific compound such as d-propoxyphene, it would be highly desirable to start with a substantially pure stereospecific precursor such as d-DAMP.
To date, there has not been a quick, efficient process for synthesizing substantially pure stereospecific d-DAMP. Previous methods in which stereospecific end products, such as d-propoxyphene, have been synthesized through stereospecific intermediates, such as d-DAMP, are lengthy procedures (e.g., reacting d-DAMP with a stereospecific tartate and benzylmagnesium chloride) in which the end product is produced inefficiently and in poor yields. A method is, therefore, needed which can synthesize stereospecific d-DAMP, quickly, efficiently, and in high yields so that this compound can be used as a precursor in the organic synthesis of d-propoxyphene.